Urolithiasis stands as a prevalent ailment in urology, with the worldwide incidence of urinary stones ranging from 1 to 20%, and specifically within China, it falls between 1 and 5% (1, 2). The global prevalence of urolithiasis has been on the rise, attributed to shifts in dietary patterns, socioeconomic factors, and climatic variations (3). Notably, the recurrence rate within a decade following treatment is notably high, hovering around 50% (4). The escalating trends in urolithiasis pose significant health threats to patients and impose substantial financial burdens. Studies forecast a projected annual increase of $1.24 billion in costs associated with urolithiasis by the year 2030 (5). This pressing issue underscores the urgent need for effective prevention strategies and treatment modalities to mitigate the impact on patient well-being and healthcare expenditures.

In recent decades, the gradual emergence of endoluminal urological techniques has significantly expanded the use of minimally invasive procedures such as percutaneous nephrolithotomy, ureteroscopy, and ureteral flexible scopes. Notably, flexible ureteroscopic lithotripsy has emerged as a safe and effective treatment option for upper urinary tract stones due to its advantages of providing a clear surgical field, minimal invasiveness, and swift recovery (6). The European Association of Urology (EAU) has endorsed this technique as the primary treatment for kidney stones measuring ≤2cm (7). Despite the benefits of these procedures, a spectrum of surgical complications can arise, with urinary sepsis representing one of the most severe, with incidence rates ranging from 0.1 to 4.3% (8). Urinary sepsis is particularly concerning due to its rapid onset, swift progression, and alarmingly high mortality rate, which can reach up to 50% (8).

A positive mid-section urine culture is closely associated with the development of urosepsis following FURL (9–11). The release of bacteria and endotoxins from within the stones during the procedure is a significant factor leading to urinary tract infections, Systemic Inflammatory Response Syndrome (SIRS), and potentially urosepsis (9). The detailed analysis of bacterial profiles holds significant clinical importance for preventing and treating postoperative urogenic sepsis. Therefore, this study aims to investigate the risk factors for urogenic sepsis following ureteral lithotripsy in patients with upper urinary tract stones, with a specific focus on preoperative urine culture results. Additionally, the study aims to analyze the clinical characteristics of various bacteria in patients who develop postoperative urogenic sepsis. The overarching goal is to provide clinicians with valuable insights and guidance for the early prevention and effective treatment of postoperative urogenic sepsis subsequent to ureteral lithotripsy using flexible ureteroscopes.

Despite advancements in urologic laparoscopic techniques and the evolution of lithotripsy and stone extraction equipment, FURL remains associated with postoperative infections, a prevalent complication (11, 14). Urogenic sepsis, as the most severe perioperative complication of FURL, continues to pose challenges for urologists in clinical practice. In this retrospective study, we identified Urine Culture, Urine Nitrite, Urine White Blood Cell count, Residual Stone, and Neutrophil-to-Lymphocyte Ratio as independent risk factors for urogenic sepsis after FURL, using univariate and multivariate logistic regression analyses. Furthermore, we conducted an analysis of bacterial distribution based on preoperative urine culture results, revealing Escherichia coli, Enterococcus faecalis, and Gardnerella vaginalis as the most common bacteria causing urinary tract infections. Understanding these prevalent urinary tract bacteria and their corresponding infection characteristics can aid in clinical diagnosis and treatment strategies.

The present study confirms that Urine culture stands as a significant risk factor for urogenic sepsis development following FURL, aligning with previous research findings (9, 10, 15, 16). Mi et al. (9) reported that 16 of 21 patients (76.2%) in the SIRS group exhibited positive preoperative urine cultures, with these results significantly correlating with postoperative SIRS development. Similarly, James et al. (17) in a retrospective analysis of 462 patients treated for stones via ureteroscopy, noted a significant association between positive mid-stream urine cultures and postoperative urinary sepsis findings, despite all patients receiving appropriate preoperative antibiotic therapy. Senocak et al. (16) in a retrospective analysis of 492 patients undergoing ureteral flexible lithotripsy, found an 8.5% incidence of postoperative infectious complications. Of the 59 patients (12%) with positive preoperative urine cultures, 19 patients (32.2%) were identified with multidrug-resistant (MDR) isolates from these cultures.

Urinary tract infections (UTIs) should be adequately treated with anti-infective therapy prior to various urologic surgeries, a consensus among major urologic guidelines. In this study, we adhered to the principles of antibiotic use outlined in the Chinese guidelines for urologic stone treatment, administering anti-infective therapy to all patients with positive preoperative urine cultures and evidence of UTIs. Despite this, 32 out of 164 patients with positive preoperative urine cultures developed urogenital sepsis, resulting in an incidence rate of 19.5%. Gutierrez et al. (9, 18) found in their study that even with the administration of broad-spectrum antibiotics to urine-negative patients or sensitive antibiotics to those with positive urine cultures, postoperative Systemic Inflammatory Response Syndrome following flexible ureteroscopic lithotripsy remained inevitable. Patients with gram-negative bacilli in their urine cultures were noted to be more prone to postoperative hyperthermia compared to those with gram-positive bacilli. It has been suggested that the biofilm formed in stones presents a challenge for antibiotics to effectively eliminate bacteria (9, 19). Despite patients with positive preoperative urine cultures exhibiting negative secondary urine cultures after antibiotic treatment and prior to surgery, the presence of bacterial endotoxins within stones complicates antibiotic penetration. Furthermore, significant endotoxin release during lithotripsy increases infection risks, potentially leading to systemic inflammatory responses. Some studies (10) suggest that early antibiotic treatment could be effective in reducing the incidence of SIRS. Considering that results from urine culture sensitivity tests typically take at least 48 hours (20), understanding common urinary tract bacteria and their respective infection characteristics becomes crucial. This understanding aids in the selection of appropriate empirical antibiotic treatment while awaiting urine culture results.

The primary bacteria identified in preoperative urine cultures in this study included Escherichia coli, Enterococcus faecalis, Gardnerella vaginalis, Proteus mirabilis, and Klebsiella pneumoniae. Among these, Escherichia coli ranked highest at 34.4%, consistent with findings from previous studies (21, 22). Cagri et al. (16) reported similar results in their study on risk factors for infectious complications following flexible ureteroscopic lithotripsy, with Escherichia coli and Enterococci being the predominant pathogens. In our study, Escherichia coli infection was notably associated with predominantly female patients and positive urinary nitrites. Furthermore, Escherichia coli positivity exhibited a significant association with postoperative urogenic sepsis after ureteral flexible lithotripsy. Patients positive for Enterococcus faecalis, Proteus mirabilis, and Klebsiella pneumoniae were also more likely to develop postoperative urogenic sepsis compared to Escherichia coli positivity (43, 33.3, and 33.3% vs. 19%). However, statistical analyses regarding postoperative urogenic sepsis were not obtained for Enterococcus faecalis and Gardnerella vaginalis, likely due to the small sample size. Studies suggest (21) that one-third of community-acquired urinary tract infections caused by Escherichia coli are attributed to ultrawide-spectrum β-lactamase (ESBL) strains, highly resistant to commonly used community antibiotics, thus limiting treatment effectiveness. Another study has shown (23) that the expression of the BLA CTX-M-14 gene in Escherichia coli leads to increased resistance, further restricting the empirical use of cephalosporins and fluoroquinolones in urinary tract infection treatment.

Enterococci are commonly identified as pathogens in urinary tract infections (24), with some studies suggesting that they have become the primary causative agent of such infections (22, 25). The main culprits among enterococci are Enterococcus faecalis Andenterococcus faecium, which are generally less virulent compared to other strains (22). In our study, Escherichia coli remained the predominant infection, with urogenic sepsis occurring in 3 out of 7 patients positive for Enterococcus faecium. Interestingly, no cases of urogenic sepsis were observed in the 10 patients with Enterococcus faecalis infections. Additionally, 66.7% of patients with Enterococcus faecium infections also had comorbid diabetes mellitus, highlighting this as a significant risk factor. Enterococci exhibit a natural resistance to many antibiotics, and there is a rapid increase in acquired resistance, complicating the treatment of urinary tract infections caused by these bacteria (26). Recent reports indicate a global rise in hospital-acquired vancomycin-resistant enterococcal infections, underscoring the potential for serious nosocomial infections (27). Therefore, heightened surveillance of this bacterial group is crucial for the prevention and control of nosocomial infections.

Proteus mirabilis and Klebsiella pneumoniae are two additional common bacteria found in our study. Studies have noted that (28) Klebsiella pneumoniae exhibits a strong adhesive and invasive capability, allowing it to persist in the urethra and resist urinary tract erosion. This resilience is particularly notable in diabetic patients with inadequate glycemic control, where the bacterium shows increased resistance and a tendency for recurrent infections. Furthermore, research has shown that (29, 30) Klebsiella pneumoniae has the ability to produce carbapenemases, acquiring resistance to carbapenems. Strains with this characteristic are also resistant to penicillin and cephalosporins, facilitating their transmission. In our study, patients who developed sepsis from Klebsiella pneumoniae infection tended to be of advanced age, with comorbid diabetes mellitus, and exhibited high Neutrophil-to-Lymphocyte Ratio, but the results were limited by the sample. Proteus mirabilis (31), a Gram-negative rod-shaped bacterium, is a prominent pathogen causing complicated urinary tract infections. Some studies have suggested that (31) catheter-associated urinary tract infections (CAUTI) in particular are the main pathogens. Due to its ureolytic biomineralization, Proteus mirabilis can form a crystalline biofilm on the surfaces of indwelling urethral catheters, leading to catheter scaling, blockage, and, often, urinary retention. This can result in ascending urinary tract infections, such as cystitis and pyelonephritis (32). This bacterium commonly coexists with various other members of the microbial community (32). A deeper understanding of Proteus mirabilis will aid clinicians in developing optimal strategies to control infections associated with this bacterium.

In addition to positive urine culture, this study identified positive urine nitrite, urine white blood cell count ≥200 cells/μL, residual stone, and Neutrophil-to-Lymphocyte Ratio as independent risk factors for urogenital sepsis following ureteral flexible lithotripsy. The urinary nitrite test and urine WBC count are commonly utilized for diagnosing urinary tract infections. Studies have indicated a high specificity of urinary nitrite for Gram-negative bacterial urinary tract infections (33). In our study, the risk of sepsis was found to be 2.74 times higher in preoperative urinary nitrite-positive patients compared to nitrite-negative patients. Moreover, debris remaining after ureteral flexible lithotripsy may harbor bacteria and endotoxins, which can enter the vasculature through damaged endothelium, potentially leading to infectious complications (34). The Neutrophil-to-Lymphocyte Ratio (35) serves as a straightforward and effective indicator of a patient’s immune status and infection severity. A retrospective study has demonstrated that (36) NLR values may be more effective than blood WBC and neutrophil counts in predicting or diagnosing urinary sepsis.

This study is subject to several limitations. Firstly, being a single-center retrospective study, it may have inherent selection bias and limited included data. A broader, prospective multicenter study is warranted for further analysis in the future. Secondly, the study did not delve into further analysis of bacterial resistance, which will be a focal point of our future research on this topic. Thirdly, intra-pelvic perfusion pressure during ureteral flexible lithotripsy is often linked to infection-related complications, yet this data was not collected in our study due to equipment limitations.

In conclusion, this study identified Urine culture positivity, Urine nitrite, Urine WBC count ≥200 cells/μL, Residual stone presence, and NLR as independent risk factors for postoperative urogenic sepsis following FURL. Additionally, the study analyzed the distribution of bacteria based on preoperative urine cultures, with Escherichia coli being the most prevalent pathogen associated with postoperative urogenic sepsis. This was followed by Enterococcus faecalis, Proteus mirabilis, and Klebsiella pneumoniae. Key characteristics of Escherichia coli infections included a higher prevalence among female patients and positive urine nitrite results. Patients with Enterococcus faecalis infections often presented with comorbid diabetes mellitus. Patients with Klebsiella pneumoniae infection and sepsis in this study were old, often complicated with diabetes, and had a high NLR. However, due to limited samples, more extensive data will need to be included in the future to further demonstrate this conclusion.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The Ethics Committee of Guizhou Hospital, Beijing Jishuitan Hospital approved this study (20220402). The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin because retrospective studies have extremely low risk.

LW: Funding acquisition, Methodology, Writing – original draft, Writing – review & editing. XY: Writing – original draft, Methodology. ZQ: Data curation, Writing – original draft. PL: Formal analysis, Writing – original draft, Supervision. WT: Supervision, Writing – original draft. WH: Investigation, Software, Writing – original draft. YP: Methodology, Validation, Writing – review & editing. FX: Project administration, Writing – review & editing. ZC: Methodology, Validation, Writing – original draft. YO: Methodology, Resources, Writing – review & editing. DL: Methodology, Project administration, Software, Supervision, Writing – original draft.